The voltage-dependent calcium channel (Ca2+ channel) mediates the entry of Ca2+ into the excitable cells, and this plays a central role in the regulation of a number of cellular functions. The Ca2+ channel is a multimeric protein complex composed of a channel forming subunits (alpha1) and several regulatory subunits. One of the regulatory subunits, termed beta, had been proven to regulate both activation and inactivation of Ca2+ channels. My general and long term objectives are to gain insight into the mechanisms that regulate Ca2+ channels. The singular focus of this research proposal is directed towards structural and functional studies of the beta subunits by using two basic tools, DNA recombinant techniques and electrophysiological techniques. The main questions addressed in this research proposal are (1) how does a beta subunit regulate Ca2+ channel properties; (2) which element(s) of the beta subunits is/are responsible for regulating activation and inactivation of Ca2+ channels: and (3) are the region(s) and residues of the beta subunit are responsible for channel modulation involved in physical contact with the channel alpha1 subunit.